Document Detail

Effects of heparin and N-acetyl heparin on ischemia/reperfusion-induced alterations in myocardial function in the rabbit isolated heart.
MedLine Citation:
PMID:  7923616     Owner:  NLM     Status:  MEDLINE    
Evidence is presented that heparin pretreatment produces protective effects on myocardial tissue distinct from its anticoagulant activity. The present study examines the ability of heparin sulfate and N-acetyl heparin (a derivative of heparin devoid of anticoagulant effects) to protect the heart from injury associated with global ischemia and reperfusion. Male New Zealand White rabbits were administered either heparin sulfate (n = 7, 300 U/kg i.v.), N-acetyl heparin (n = 6, 1.73 mg/kg i.v.), or vehicle (n = 6). Two hours after treatment, the hearts were removed, perfused on a Langendorff apparatus, and subjected to 30 minutes of global ischemia, followed by 45 minutes of reperfusion. During reperfusion, creatine kinase concentrations in the coronary sinus effluent were greater in hearts from vehicle-treated rabbits compared with hearts from N-acetyl heparin-treated and heparin-treated rabbits. Left ventricular end-diastolic pressure after 45 minutes of reperfusion in the vehicle-treated group was 64 +/- 15 mm Hg compared with 17 +/- 4 and 10 +/- 3 mm Hg in the heparin-pretreated and N-acetyl heparin-pretreated groups, respectively. Heparin, but not N-acetyl heparin, increased the activated partial thromboplastin time, consistent with its known anticoagulant action. Heparin and N-acetyl heparin inhibited complement-mediated erythrocyte lysis in a concentration-dependent manner. The glycosaminoglycans, in contrast to r-hirudin, reduced complement activation-induced injury in the rabbit isolated heart. The results demonstrate that heparin or N-acetyl heparin, administered to the intact rabbit, protects the isolated heart from subsequent myocardial dysfunction secondary to ischemia/reperfusion. The cardioprotective effects of heparin and N-acetyl heparin are independent of an antithrombin mechanism.
G S Friedrichs; K S Kilgore; P J Manley; M R Gralinski; B R Lucchesi
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  75     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1994 Oct 
Date Detail:
Created Date:  1994-10-26     Completed Date:  1994-10-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  701-10     Citation Subset:  IM    
University of Michigan Medical School, Department of Pharmacology, Ann Arbor 48109-0626.
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MeSH Terms
Calcium / metabolism
Creatine Kinase / blood
Glycosaminoglycans / metabolism
Heart / drug effects*
Heparin / analogs & derivatives*,  pharmacology*
Myocardial Ischemia* / physiopathology
Myocardial Reperfusion Injury / prevention & control*
Myocardium / metabolism
Partial Thromboplastin Time
Time Factors
Grant Support
Reg. No./Substance:
0/Glycosaminoglycans; 134498-62-7/N-acetylheparin; 7440-70-2/Calcium; 9005-49-6/Heparin; EC Kinase

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